Nerve Growth Factor (NGF) is necessary for the normal development and survival of nerve cells in the peripheral and central nervous system. The cellular mechanisms through which NGF elicits its effects are unknown. The discovery of a protein kinase, which is activated by NGF, may play an important role as a transducer of signals derived from NGF's interaction with cell receptors. Dr. Landreth has previously characterized and purified this protein kinase known as MAP2 by the enzyme's ability to phosphorylate microtubule associated protein 2. This research project will determine how the protein kinase is activated. It has been established that MAP2 kinase is activated through phosphorylation by an unidentified kinase. The mechanism of MAP2 kinase activation will be investigated by transfecting PC12 cells with oncogenes that encode kinases for the amino acids serine and threonine. The biological function of MAP2 kinase will be studied by creating mutant cells which lack MAP2 kinase. This will be accomplished by utilizing antisense RNA or DNA molecules which specifically block the synthesis of the MAP2 kinase. This examination will analyze whether kinase deficient cells respond to NGF by activation of other protein kinases. Results from this study will provide additional information on the function of NGF in the nervous system.
